Summary"Digital communication permeates all areas of today's daily life. Cryptographic protocols are used to secure that
communication. Quantum communication and the advent of quantum computers both threaten existing cryptographic
solutions, and create new opportunities for secure protocols. The security of cryptographic systems is normally ensured by
mathematical proofs. Due to human error, however, these proofs often contain errors, limiting the usefulness of said proofs.
This is especially true in the case of quantum protocols since human intuition is well-adapted to the classical world, but not
to quantum mechanics. To resolve this problem, methods for verifying cryptographic security proofs using computers (i.e.,
for ""certifying"" the security) have been developed. Yet, all existing verification approaches handle classical cryptography
only - for quantum protocols, no approaches exist.
This project will lay the foundations for the verification of quantum cryptography. We will design logics and software tools
for developing and verifying security proofs on the computer, both for classical protocols secure against quantum computer
(post-quantum security) and for protocols that use quantum communication.
Our main approach is the design of a logic (quantum relational Hoare logic, qRHL) for reasoning about the relationship
between pairs of quantum programs, together with an ecosystem of manual and automated reasoning tools, culminating in
fully certified security proofs for real-world quantum protocols.
As a final result, the project will improve the security of protocols in the quantum age, by removing one possible source of
human error. In addition, the project directly impacts the research community, by providing new foundations in program
verification, and by providing cryptographers with new tools for the verification of their protocols.
"

"Digital communication permeates all areas of today's daily life. Cryptographic protocols are used to secure that
communication. Quantum communication and the advent of quantum computers both threaten existing cryptographic
solutions, and create new opportunities for secure protocols. The security of cryptographic systems is normally ensured by
mathematical proofs. Due to human error, however, these proofs often contain errors, limiting the usefulness of said proofs.
This is especially true in the case of quantum protocols since human intuition is well-adapted to the classical world, but not
to quantum mechanics. To resolve this problem, methods for verifying cryptographic security proofs using computers (i.e.,
for ""certifying"" the security) have been developed. Yet, all existing verification approaches handle classical cryptography
only - for quantum protocols, no approaches exist.
This project will lay the foundations for the verification of quantum cryptography. We will design logics and software tools
for developing and verifying security proofs on the computer, both for classical protocols secure against quantum computer
(post-quantum security) and for protocols that use quantum communication.
Our main approach is the design of a logic (quantum relational Hoare logic, qRHL) for reasoning about the relationship
between pairs of quantum programs, together with an ecosystem of manual and automated reasoning tools, culminating in
fully certified security proofs for real-world quantum protocols.
As a final result, the project will improve the security of protocols in the quantum age, by removing one possible source of
human error. In addition, the project directly impacts the research community, by providing new foundations in program
verification, and by providing cryptographers with new tools for the verification of their protocols.
"

SummaryMultisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal in this application is to elucidate the molecular basis of this important mechanism. We recently demonstrated a novel phenomenon of multisite phosphorylation in cell cycle regulation. We showed that cyclin-dependent kinase (CDK)-dependent multisite phosphorylation of a crucial substrate is performed semiprocessively in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation networks along the disordered protein segments determine the net phosphorylation rate of the protein. This concept provides a new interpretation of CDK signal processing, and it can explain how the temporal order of cell cycle events is achieved. The goals of this study are: 1) We will seek proof of the model by rewiring the patterns of budding yeast Cdk1 multisite networks according to the rules we have identified, so to change the order of cell cycle events. Next, we will restore the order by alternative wiring of the same switches; 2) To apply the proposed model in the context of different kinases and complex substrate arrangements, we will study the Cdk1-dependent multisite phosphorylation of kinetochore components, to understand the phospho-regulation of kinetochore formation, microtubule attachment and error correction; 3) We will apply multisite phosphorylation to design circuits for synthetic biology. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field since the fast time scales and wide combinatorial possibilities.

Multisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal in this application is to elucidate the molecular basis of this important mechanism. We recently demonstrated a novel phenomenon of multisite phosphorylation in cell cycle regulation. We showed that cyclin-dependent kinase (CDK)-dependent multisite phosphorylation of a crucial substrate is performed semiprocessively in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation networks along the disordered protein segments determine the net phosphorylation rate of the protein. This concept provides a new interpretation of CDK signal processing, and it can explain how the temporal order of cell cycle events is achieved. The goals of this study are: 1) We will seek proof of the model by rewiring the patterns of budding yeast Cdk1 multisite networks according to the rules we have identified, so to change the order of cell cycle events. Next, we will restore the order by alternative wiring of the same switches; 2) To apply the proposed model in the context of different kinases and complex substrate arrangements, we will study the Cdk1-dependent multisite phosphorylation of kinetochore components, to understand the phospho-regulation of kinetochore formation, microtubule attachment and error correction; 3) We will apply multisite phosphorylation to design circuits for synthetic biology. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field since the fast time scales and wide combinatorial possibilities.